• Jiayi Wu, Yangui Wang, Wugeng Cui, Wenhua Zhou, and Xin Zhao.
• Department of Pharmacology, Ningbo University, School of Medical Science, Ningbo, China.
• Reg Anesth Pain Med. 2020 Aug 1; 45 (8): 610-619.

BackgroundPersistent neuropathic pain poses a health problem, for which effective therapy or antidote is in dire need. This work aimed to investigate the pain-relieving effect of chrysin, a natural flavonoid with monoamine oxidase inhibitory activity, in an experimental model of neuropathic pain and elucidate mechanism(s).MethodsChronic constriction injury (CCI) was produced by loose ligation of sciatic nerve in mice. The pain-related behaviors were examined using von Frey test and Hargreaves test. The serotonin-related mechanisms were investigated by serotonin depletion with p-chlorophenylalanine (PCPA) and antagonist tests in vivo and in vitro.ResultsRepeated treatment of CCI mice with chrysin (orally, two times per day for 2 weeks) ameliorated heat hyperalgesia and mechanical allodynia in a dose-dependent fashion (3-30 mg/kg). The chrysin-triggered pain relief seems serotonergically dependent, since its antihyperalgesic and antiallodynic actions were abolished by chemical depletion of serotonin by PCPA, whereas potentiated by 5-hydroxytryptophan (a precursor of 5-HT). Consistently, chrysin-treated neuropathic mice showed enhanced levels of spinal monoamines especially 5-HT, with depressed monoamine oxidase activity. Moreover, chrysin-evoked pain relief was preferentially counteracted by 5-HT1A receptor antagonist WAY-100635 delivered systematically or spinally. In vitro, chrysin (0.1-10 nM) increased the maximum effect (Emax, shown as stimulation of [35S] GTPγS binding) of 8-OH-DPAT, a 5-HT1A agonist. Beneficially, chrysin was able to correct comorbid behavioral symptoms of depression and anxiety evoked by neuropathic pain, without causing hypertensive crisis (known as 'cheese reaction').ConclusionThese findings confirm the antihyperalgesic and antiallodynic efficacies of chrysin, with spinal 5-HT1A receptors being critically engaged.© American Society of Regional Anesthesia & Pain Medicine 2020. No commercial re-use. See rights and permissions. Published by BMJ.

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